Doernbecher Children's Hospital

Davare Lab

Translational research interests

Our broad research objectives are to discover cell intrinsic pathways that promote oncogenesis and malignant progression of tumors, with a special interest in rare but aggressive pediatric and adult tumors. Concomitantly we identify and test effective, targeted pharmacological agents that are amenable for clinical implementation as cancer treatments. Associated efforts to identify mechanisms of clinical resistance pre-emptively, and discover second-line therapies have permitted us to bridge bench research to clinical trials. Close collaborations with clinical colleagues at OHSU and across the US have facilitated progress and success of our translational research interests. Ultimately, we hope to expand the utility of targeted treatments via the discovery of new response biomarkers, and importantly, extend the durability of these molecularly targeted therapies by mitigating resistance pathways.

Basic research interests

We also are avid basic scientists working to describe the function and regulation of gene products that remain poorly characterized and understood. Currently, we have an overarching interest in elucidating the biological role and biochemical regulation of ROS1 in cancer cells as well as normal human cell and tissue function. We are using several approaches, including structure-functional analysis, loss- and gain-of-function assays, as well as pharmacological inhibition to elucidate functional impact of missense mutations on ROS1 catalytic activity, and mechanisms of receptor homeostasis.

Current projects in the lab include

  • Functional impact of somatic ROS1 aberrations discovered in cancer patients
  • Effectively targeting ROS1, NTRK, and ALK fusion proteins in cancer
  • Pre-emptive prediction of resistance to targeted therapy and validation of novel resistance mechanisms in ROS1 and NTRK driven cancers
  • Role of ROS1 in glioblastoma
  • Discovery of novel compounds to target Ewing's sarcoma
  • Physiological regulation of and by ROS1 in human lung